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17 results on '"Slutske, W.S."'

1. Genome-wide association study of pathological gambling

Author

Lang, M., Leménager, T., Streit, F., Fauth-Bühler, M., Frank, J., Juraeva, D., Witt, S.H., Degenhardt, F., Hofmann, A., Heilmann-Heimbach, S., Kiefer, F., Brors, B., Grabe, H.-J., John, U., Bischof, A., Bischof, G., Völker, U., Homuth, G., Beutel, M., Lind, P.A., Medland, S.E., Slutske, W.S., Martin, N.G., Völzke, H., Nöthen, M.M., Meyer, C., Rumpf, H.-J., Wurst, F.M., Rietschel, M., and Mann, K.F.

Published
2016
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2. Genetic and environmental contributions to variance in age at first sexual intercourse

Author

Dunne, M.P., Martin, N.G., Statham, D.J., Slutske, W.S., Dinwiddie, S.H., Bucholz, K.K., Madden, P.A.F., and Heath, A.C.

Subjects
Sexual intercourse -- Demographic aspects, Sexual behavior surveys -- Statistics, Twins -- Sexual behavior, Psychology and mental health
Abstract

Little is known about the relative importance of genetic and environmental factors as determinants of age at first sexual intercourse. In this study, subjects were 5,080 individuals from the Australian Twin Registry (3,310 females, 1,770 males; age range: 27-70 years, median: 40 years) who completed a semistructured interview by telephone in 1992-1993. Self-reported age at first intercourse correlated higher for identical (monozygotic) twins than for nonidentical (dizygotic) twins. Structural equation model fitting found that the genetic contribution to variance was considerably greater among twins aged 40 years or less (72% for males and 49% for females) than for those aged from 41 to 70 years (0%for males and 32% for females). Among the older cohort, there was evidence that somewhat different aspects of the shared social environment influenced age at onset in males and females. In a more laissez-faire social climate in recent decades, it is likely that biological and psychological characteristics that are partly under genetic control significantly influence the age at which a person commences sexual activity., Age at first sexual intercourse is probably greatly influenced in modern times by psychological and biological factors that are partly controlled genetically because social constraints are less than before. Influences on the age of commencement of sexual activity appear to have been different among research subjects aged 41- to 70-years-old than for those aged under 40. Age at first intercourse correlated lower for nonidentical twins than identical twins, with the variance more genetically affected for twins aged under 40 than for those aged 41-70.

Published
1997

3. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author

Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., et al., Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., and et al.

Abstract

Contains fulltext : 166013.pdf (publisher's version ) (Open Access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Published
2016

4. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author

Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)

Abstract

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Published
2016
Full Text
View/download PDF

5. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

van den Berg, S.M., de Moor, M.H.M., McGue, M., Pettersson, E., Terracciano, A., Verweij, C.J.H., Amin, N., Derringer, J., Esko, T., Grootheest, G., Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., de Geus, E.J.C., Giegling, I., Gow, A. J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J., Jokela, M, Kiemeney, L., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Pulkki-Råback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J, Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Räikkönen, K., Arias-Vasquez, A., Costa, P.T., Keltikangas-Järvinen, L., van Duijn, C.M., Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Biological Psychology, Clinical Child and Family Studies, EMGO+ - Mental Health, Psychiatry, and EMGO - Mental health

Subjects
Netherlands Twin Register (NTR)
Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. © 2014 The Author(s).

Published
2014

6. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author

Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.

Abstract

Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.

Published
2015

7. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

Author

Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)

Abstract

IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P <.05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identi

Published
2015
Full Text
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8. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.

Abstract

Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Published
2014

9. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author

Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)

Abstract

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Published
2014
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11. The genetics of addiction: A translational perspective

Author

Agrawal, A., Verweij, K.J.H., Gillespie, N.A., Heath, A.C., Lessov-Schlaggar, C.N., Martin, N.G., Nelson, E.C., Slutske, W.S., Whitfield, J.B., Lynskey, M.T., Agrawal, A., Verweij, K.J.H., Gillespie, N.A., Heath, A.C., Lessov-Schlaggar, C.N., Martin, N.G., Nelson, E.C., Slutske, W.S., Whitfield, J.B., and Lynskey, M.T.

Abstract

Contains fulltext : 156134.pdf (publisher's version ) (Open Access), Addictions are serious and common psychiatric disorders, and are among the leading contributors to preventable death. This selective review outlines and highlights the need for a multi-method translational approach to genetic studies of these important conditions, including both licit (alcohol, nicotine) and illicit (cannabis, cocaine, opiates) drug addictions and the behavioral addiction of disordered gambling. First, we review existing knowledge from twin studies that indicates both the substantial heritability of substance-specific addictions and the genetic overlap across addiction to different substances. Next, we discuss the limited number of candidate genes which have shown consistent replication, and the implications of emerging genomewide association findings for the genetic architecture of addictions. Finally, we review the utility of extensions to existing methods such as novel phenotyping, including the use of endophenotypes, biomarkers and neuroimaging outcomes; emerging methods for identifying alternative sources of genetic variation and accompanying statistical methodologies to interpret them; the role of gene-environment interplay; and importantly, the potential role of genetic variation in suggesting new alternatives for treatment of addictions.

Published
2012

12. The genetics of smoking initiation and quantity smoked in Dutch adolescent and young adult twins

Author

Koopmans, J.R., Slutske, W.S., Heath, A.C., Neale, M.C., Boomsma, D.I., and Biological Psychology

Subjects
Netherlands Twin Register (NTR), SDG 3 - Good Health and Well-being
Abstract

Not much is known about the genetic and environmental determinants of various aspects of substance use in adolescents. This study examined whether the inheritance of initiation of tobacco use in adolescents is independent of the inheritance of the number of cigarettes smoked. Alternative multifactorial threshold models were applied to data on tobacco use in 1676 Dutch adolescent twin pairs. The three models that were considered are (i) the single liability dimension model, (ii) the independent liability dimension model, and (iii) the combined model (CM). The results showed that there is not one underlying continuum of liability to smoking. The CM was the best-fitting model. This model postulates that there are separate initiation and quantity dimensions but allows for the possibility that there are some individuals who are so low on the liability to level of consumption that they are not using tobacco. There were no differences between males and females in the magnitude of the genetic and environmental influences on individual differences in smoking initiation and quantity smoked. Smoking initiation was influenced by genetic factors (39%) and shared environmental influences (54%). Once smoking is initiated genetic factors determine to a large extent (86%) the quantity that is smoked.

Published
1999

13. The Influence of Religion on Alcohol Use Initiation: Evidence for Genotype X Environment Interaction

Author

Koopmans, J.R., Slutske, W.S., van Baal, G.C.M., Boomsma, D.I., and Biological Psychology

Subjects
Netherlands Twin Register (NTR)
Abstract

We examined the possible role of religious upbringing as a mediator of the shared environmental influences and as a moderator of the genetic influences on the risk of alcohol use initiation in a large population-based sample of Dutch adolescent and young adult twins (1967 twin pairs). There was not a significant association between religious participation and alcohol use initiation among Dutch adolescents and young adults. We also hypothesized that the relative magnitude of the genetic influences on the risk of alcohol use initiation would be greater for those adolescents and young adults who were raised in a less religious environment compared to those adolescents and young adults who were raised in a more religious environment. We indeed found higher heritabilities for females without a religious upbringing compared to females with a religious upbringing. Genetic influences accounted for 40% of the variance in alcohol use initiation in nonreligious females, compared to 0% in religiously raised females. Shared environmental influences accounted for 54% of the variance for nonreligious females and 88% of the variance in religious females. For males, the genetic variance was also higher in the nonreligious group compared to the religious group, but this difference was not statistically significant. Whether or not they were raised religiously, the liability to alcohol use initiation in males was moderately influenced by genetic factors (30%) and substantially influenced by shared environmental factors (60%).

Published
1999

15. An Integrative Approach for Studying the Etiology of Alcoholism and Other Addictions

Author

Jacob, T., primary, Sher, K.J., additional, Bucholz, K.K., additional, True, W.T., additional, Sirevaag, E.J., additional, Rohrbaugh, J., additional, Nelson, E., additional, Neuman, R.J., additional, Todd, R.D., additional, Slutske, W.S., additional, Whitfield, J.B., additional, Kirk, K.M., additional, Martin, N.G., additional, Madden, P.A.F., additional, and Heath, A.C., additional

Published
2001
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